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Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination.


ABSTRACT: Zika virus (ZIKV) has recently emerged as a pandemic associated with severe neuropathology in newborns and adults. There are no ZIKV-specific treatments or preventatives. Therefore, the development of a safe and effective vaccine is a high priority. Messenger RNA (mRNA) has emerged as a versatile and highly effective platform to deliver vaccine antigens and therapeutic proteins. Here we demonstrate that a single low-dose intradermal immunization with lipid-nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) encoding the pre-membrane and envelope glycoproteins of a strain from the ZIKV outbreak in 2013 elicited potent and durable neutralizing antibody responses in mice and non-human primates. Immunization with 30??g of nucleoside-modified ZIKV mRNA-LNP protected mice against ZIKV challenges at 2 weeks or 5 months after vaccination, and a single dose of 50??g was sufficient to protect non-human primates against a challenge at 5 weeks after vaccination. These data demonstrate that nucleoside-modified mRNA-LNP elicits rapid and durable protective immunity and therefore represents a new and promising vaccine candidate for the global fight against ZIKV.

SUBMITTER: Pardi N 

PROVIDER: S-EPMC5344708 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination.

Pardi Norbert N   Hogan Michael J MJ   Pelc Rebecca S RS   Muramatsu Hiromi H   Andersen Hanne H   DeMaso Christina R CR   Dowd Kimberly A KA   Sutherland Laura L LL   Scearce Richard M RM   Parks Robert R   Wagner Wendeline W   Granados Alex A   Greenhouse Jack J   Walker Michelle M   Willis Elinor E   Yu Jae-Sung JS   McGee Charles E CE   Sempowski Gregory D GD   Mui Barbara L BL   Tam Ying K YK   Huang Yan-Jang YJ   Vanlandingham Dana D   Holmes Veronica M VM   Balachandran Harikrishnan H   Sahu Sujata S   Lifton Michelle M   Higgs Stephen S   Hensley Scott E SE   Madden Thomas D TD   Hope Michael J MJ   Karikó Katalin K   Santra Sampa S   Graham Barney S BS   Lewis Mark G MG   Pierson Theodore C TC   Haynes Barton F BF   Weissman Drew D  

Nature 20170202 7644


Zika virus (ZIKV) has recently emerged as a pandemic associated with severe neuropathology in newborns and adults. There are no ZIKV-specific treatments or preventatives. Therefore, the development of a safe and effective vaccine is a high priority. Messenger RNA (mRNA) has emerged as a versatile and highly effective platform to deliver vaccine antigens and therapeutic proteins. Here we demonstrate that a single low-dose intradermal immunization with lipid-nanoparticle-encapsulated nucleoside-mo  ...[more]

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